Chronic Hepatitis B is a severe infectious disease widely prevalent throughout the world, which is caused by hepatitis B virus (HBV) and is closely associated with occurrence of hepatocirrhosis and liver cancer. China is a high prevalence area of Hepatitis B. The results of nationally seropidemiological survey of viral hepatitis in China from 1992 to 1995 showed that the persons carrying viral hepatitis B surface antigen (HBsAg) in China accounted for 9.7% of the population, and it was estimated that there are 1.3×108 HBV carriers. The study on the epidemic situation of viral hepatitis in China showed that the annual reported morbidity of hepatitis B increased from 21.9/100,000 in 1990 to 53.3/100,000 in 2003, which exhibited an obvious ascending trendency (see: Wang Xiaojun, Zhang Rongzhen and Hu Yuansheng et al, Disease Monitoring, 2004, 19(8): 290-292). Chronic Hepatitis B not only seriously affects the health of human body but also imposes heavy economic burden on family and society. Chronic Hepatitis B has become one of significant public health problems in China.
Drugs for the treatment of Chronic Hepatitis B usually belong to two main classes, i.e. immunomodulators and nucleoside DNA polymerase inhibitors (Loomba R., Liang T. J., Antivir. Ther., 2006, 11(1): 1-15), in which the former includes interferon-α2b (IFN-α2b, Intron A®) and Pegylated interferon-α2a (peg IFN-α2a, Pegasys®), while the latter includes Lamivudine (EPivir-HBV®), Adefovir Dipivoxil (Hepsera®) and Entecavir (Baraclude®). Comparatively speaking, there are quite few of drugs in number and class for the clinical treatment of Hepatitis B. Therefore, it is of high significance to research and develop novel, safe and effective antiviral drugs, in particular those having a completely new mechanism of action.
Quinazolinone compounds have a wide range of physiological activities, for example, they can be used as adrenoceptor regulators (WO2005005397) and estrogen receptor regulators (WO2006116401). In the meantime, 2(1H)- and 4(1H)-quinazolinone compounds further have activities such as pyretolysis, analgesic and anti-inflammatory activity (GB1308198, U.S. Pat. No. 3,895,395, JP57011970), and 4(3H)-quinazolinone compounds have anti-ulcer activity (EP0276826). However, no report has been found relating to 5(1H)-quinazolinone compounds.